Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 4030030, China.
The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China.
Mol Neurobiol. 2019 May;56(5):3368-3379. doi: 10.1007/s12035-018-1312-5. Epub 2018 Aug 17.
Loss of memory is an inevitable clinic sign in aging, but its underlying mechanisms remain unclear. Here we show that death-associated protein kinase (DAPK1) is involved in the decays of learning and memory in aging via degradation of Caytaxin, a brain-specific member of BNIP-2. DAPK1 becomes activated in the hippocampus of mice during aging. Activation of DAPK1 is closely associated with degradation of Caytaxin protein. Silencing Caytaxin by the expression of small interfering RNA (siRNA) that targets specifically to Caytaxin in the hippocampus of adult mice impairs the learning and memory. Genetic inactivation of DAPK1 by deletion of DAPK1 kinase domain prevents the degradation of Caytaxin and protects against learning and memory declines. Thus, activation of DAPK1 impairs learning and memory by degrading Caytaxin during aging.
记忆丧失是衰老过程中不可避免的临床特征，但其中的潜在机制仍不清楚。在这里，我们发现死亡相关蛋白激酶（DAPK1）通过降解脑特异性 BNIP-2 家族成员 Caytaxin 参与衰老过程中学习和记忆的衰退。在衰老过程中，DAPK1 在小鼠海马体中被激活。DAPK1 的激活与 Caytaxin 蛋白的降解密切相关。通过在成年小鼠海马体中表达针对 Caytaxin 的小干扰 RNA（siRNA）特异性沉默 Caytaxin，会损害学习和记忆能力。通过删除 DAPK1 激酶结构域使 DAPK1 基因失活，可防止 Caytaxin 降解并防止学习和记忆能力下降。因此，在衰老过程中，DAPK1 通过降解 Caytaxin 来损害学习和记忆。
